The major objective of the proposed research is to effect an in-depth biochemical study of the major catalytic components of the insect microsomal enzymes responsible for drug and insecticide metabolism. Emphasis will be placed on the solubilization purification and characterization of the microsomal cytochrome P-450, NADPH cytochrome c (P-450) reductase and cytochrome b5 in midgut microsomes from the southern armyworm (Spodoptera eridania). The properties of these components as well as that of the lipid fraction will be compared with the corresponding components from mammalian hepatic microsomes. The proposed comparative studies involve establishing immunological cross-reactivity patterns and attempts to cross-reconstitute the various solubilized components from insects and mammals. The possible existence of multiple forms of cytochrome P-450 in the southern armyworm will be investigated in control and induced larvae. The role of cytochrome b5 in insect microsomal oxidation will be investigated. The potential involvement of specific DNA-dependent RNA polymerases (I, II and III) in the induction mechanism will be investigated by the use of specific inhibitors and templates. The properties of the soluble, highly purified epoxide hydrase from the armyworm midgut will be determined and compared with that from mammalian liver with respect to composition, substrate specificity, inhibitor susceptibility and mechanism.